WO2004076443A1 - Forme amorphe de potassium de losartan - Google Patents

Forme amorphe de potassium de losartan Download PDF

Info

Publication number
WO2004076443A1
WO2004076443A1 PCT/IN2003/000037 IN0300037W WO2004076443A1 WO 2004076443 A1 WO2004076443 A1 WO 2004076443A1 IN 0300037 W IN0300037 W IN 0300037W WO 2004076443 A1 WO2004076443 A1 WO 2004076443A1
Authority
WO
WIPO (PCT)
Prior art keywords
losartan potassium
amorphous form
alcohol
ethanol
substantially amorphous
Prior art date
Application number
PCT/IN2003/000037
Other languages
English (en)
Inventor
Reddy Bandi Parthasaradhi
Reddy Kura Rathnakar
Reddy Rapolu Raji
Reddy Attunuri Narasa
Reddy Bolla Narasa
Original Assignee
Hetero Drugs Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hetero Drugs Limited filed Critical Hetero Drugs Limited
Priority to AU2003209669A priority Critical patent/AU2003209669A1/en
Priority to PCT/IN2003/000037 priority patent/WO2004076443A1/fr
Publication of WO2004076443A1 publication Critical patent/WO2004076443A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin

Definitions

  • the invention relates to a novel amorphous form of losartan potassium, to a process for the preparation thereof and to a composition containing it.
  • Losartan potassium is known by the chemical name 2-butyl-4-chloro-1- [[2'-(1H- tetrazol-5-yl)[1,1'-biphenyl]-4-yl] methyl]-1 H-imidazole-5-methanol mono- potassium salt.
  • Losartan potassium is an antihypertensive agent having a superior antagonistic activity against angiotensin II.
  • Losartan and its potassium salt may be prepared using the procedures described in Eur. pat. No. 324377, 253310, 470794, 495626, WO 95/26188 and WO
  • U.S. pat. No. 5,859,258 describes a crystallization process for losartan potassium to obtain the desired crystal morphology and bulk physical properties necessary for formulation.
  • U.S. pat. No. 6,350,880 describes crystallization procedures of losartan potassium as a purification method for obtaining highly pure losartan potassium.
  • losartan potassium occurs in two crystalline forms, Form I and Form II.
  • the existence of amorphous form of losartan has now been discovered.
  • losartan potassium in substantially amorphous form has higher bioavailability than when in crystalline form and that moreover the amorphous form of losartan potassium has adequate chemical stability upon storage and therefore can be used in pharmaceutical formulation.
  • the object of present invention is to provide a novel amorphous form of losartan potassium (herein after referred to as amorphous losartan potassium), process for preparation thereof and a pharmaceutical composition containing it.
  • Figure 1 is a powder x-ray diffractogram of amorphous losartan potassium.
  • Powder x-ray diffraction pattern was measured on a Siemens D-5000 diffractometer with CuKr radiation.
  • losartan potassium in substantially amorphous form.
  • Any residual solvent present will desirably only be present in less than 4% mass/mass (m/m) and most preferably less than 1% m/m.
  • Typical powder x-ray diffraction pattern of amorphous losartan potassium is shown in fig.1.
  • the amorphous losartan potassium according to the invention is prepared by a process which constitutes a further feature of the present invention and which comprises recovering losartan potassium from a solution thereof under conditions whereby a substantially amorphous product is obtained.
  • Techniques which are employed to recover amorphous losartan potassium from the solution thereof include those wherein solvent is removed from the solution and the product deposited. Methods involving the use of these procedures include spray drying and vacuum drying. Suitable solvents for dissolving losartan potassium to form solutions from which recovery is possible include alcohols; if desired mixed with others solvents. Alcohols include methanol and ethanol; and the term 'other solvents' refers to ethylacetate, chloroform and methylene dichloride. Preferred solvents are methanol or ethanol mixed with ethylacetate or chloroform.
  • the alcohol to other solvent ratio is preferably between about 1 : 0.2 to about 1 : 2 and most preferably between about 1 : 1 to about 1 : 1.8.
  • the concentration of losartan potassium in the solvent or the mixed solvent mixture required to form amorphous form of losartan potassium depends on the solvent or the solvent mixture used, preferred concentrations being greater than 5% mass/mass (m/m).
  • the maximum concentration of the losartan potassium depends on the solvent or solvent mixture used.
  • the solvents may if desired be heated as an aid for solubility and partial removal of solvent. In carrying out the spray drying technique, it is highly desirable that the boiling point of the solvent employed will lie below the coagulation point of the product of the invention under the conditions used.
  • losartan potassium solution is dried under vacuum in the temperature range of 25-50°C, preferable range being 35-40°C.
  • crystalline form I, and form II of losartan potassium is used for preparing amorphous losartan potassium.
  • the crystalline forms (form I and form II) may be obtained by the processes described in ' US pat No. 5,608,075.
  • Another feature of the present invention is to provide a pharmaceutical composition comprising amorphous losartan potassium.
  • compositions containing amorphous losartan potassium may be in a form suitable for oral dosage as a tablet, capsule, suspension. Any conventional technique may be used for the preparation of pharmaceutical formulation according to the invention.
  • suitable diluents are lactose, micro crystalline cellulose, starch, mannitol.
  • binders are polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl hydroxy propyl cellulose.
  • suitable disintigrants are sodium starch glycollate, crospovidone, croscarmellose sodium.
  • Example-1 Losartan potassium crystals (50 gm) are added to the mixture containing methanol (100 ml) and ethylacetate (150 ml) and stirred for 1 hour to dissolve. The solution is dried under vacuum at 35-40°C for 18 hours to give 42 gm of amorphous losartan potassium.
  • Example-2 is repeated using 50 gm of losartan potassium Form-I.
  • Example-3 Losartan potassium crystals (30 gm) are dissolved in the mixture containing ethanol (100 ml) and chloroform (120 ml). The solution obtained is spray dried to obtain 22.5 gm of amorphous losartan potassium.
  • Example-4 Losartan potassium crystals (30 gm) are dissolved in the mixture containing ethanol (100 ml) and chloroform (120 ml). The solution obtained is spray dried to obtain 22.5 gm of amorphous losartan potassium.
  • Example-4 Losartan potassium crystals (30 gm) are dissolved in the mixture containing ethanol (100 ml) and chloroform (120 ml). The solution obtained is spray dried to obtain 22.5 gm of amorphous losartan potassium.
  • Example-4 Losartan potassium crystals (30 gm) are dissolved in the mixture containing ethanol (100 ml) and chloroform (120 ml). The solution obtained is spray dried to obtain 22.5 gm of amorphous losartan potassium.
  • Emample-3 is repeated using losartan potassium Form-ll.

Abstract

Cette invention se rapporte à une nouvelle forme amorphe de potassium de losartan, à un procédé de préparation de celle-ci, et à une composition la contenant.
PCT/IN2003/000037 2003-02-25 2003-02-25 Forme amorphe de potassium de losartan WO2004076443A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003209669A AU2003209669A1 (en) 2003-02-25 2003-02-25 Amorphous form of losartan potassium
PCT/IN2003/000037 WO2004076443A1 (fr) 2003-02-25 2003-02-25 Forme amorphe de potassium de losartan

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2003/000037 WO2004076443A1 (fr) 2003-02-25 2003-02-25 Forme amorphe de potassium de losartan

Publications (1)

Publication Number Publication Date
WO2004076443A1 true WO2004076443A1 (fr) 2004-09-10

Family

ID=32922922

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2003/000037 WO2004076443A1 (fr) 2003-02-25 2003-02-25 Forme amorphe de potassium de losartan

Country Status (2)

Country Link
AU (1) AU2003209669A1 (fr)
WO (1) WO2004076443A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006076097A2 (fr) * 2004-12-07 2006-07-20 Nektar Therapeutics Preparation non cristalline stable contenant du losartan
US8530488B2 (en) 2007-10-24 2013-09-10 Generics [Uk] Limited Crystalline forms of bosentan
US8664390B2 (en) 2007-06-29 2014-03-04 Generics (Uk) Limited Process for the introduction of hydroxyethoxy side chain in bosentan
US8785461B2 (en) 2008-02-08 2014-07-22 Generics [Uk] Limited Process for preparing bosentan
US8975402B2 (en) 2008-11-03 2015-03-10 Generics [Uk] Limited HPLC method for the analysis of bosetan and related substances and use of these substances as reference standards and markers
JP2016535767A (ja) * 2013-11-01 2016-11-17 深▲せん▼信立泰藥業股▲ふん▼有限公司 アリサルタン・イソプロキシル非晶形とその調製方法及びその非晶形を含む医薬組成物

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5140037A (en) * 1990-03-20 1992-08-18 E. I. Du Pont De Nemours And Company Treatment of central nervous system disorders with imidazole angiotensin-ii receptor antagonists
WO2003048135A1 (fr) * 2001-11-14 2003-06-12 Teva Pharmaceutical Industries Ltd. Formes cristallines amorphes de losartan potassique et leur procede de preparation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5140037A (en) * 1990-03-20 1992-08-18 E. I. Du Pont De Nemours And Company Treatment of central nervous system disorders with imidazole angiotensin-ii receptor antagonists
WO2003048135A1 (fr) * 2001-11-14 2003-06-12 Teva Pharmaceutical Industries Ltd. Formes cristallines amorphes de losartan potassique et leur procede de preparation

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006076097A2 (fr) * 2004-12-07 2006-07-20 Nektar Therapeutics Preparation non cristalline stable contenant du losartan
WO2006076097A3 (fr) * 2004-12-07 2006-09-14 Nektar Therapeutics Preparation non cristalline stable contenant du losartan
US8664390B2 (en) 2007-06-29 2014-03-04 Generics (Uk) Limited Process for the introduction of hydroxyethoxy side chain in bosentan
US8530488B2 (en) 2007-10-24 2013-09-10 Generics [Uk] Limited Crystalline forms of bosentan
US8785461B2 (en) 2008-02-08 2014-07-22 Generics [Uk] Limited Process for preparing bosentan
US8975402B2 (en) 2008-11-03 2015-03-10 Generics [Uk] Limited HPLC method for the analysis of bosetan and related substances and use of these substances as reference standards and markers
JP2016535767A (ja) * 2013-11-01 2016-11-17 深▲せん▼信立泰藥業股▲ふん▼有限公司 アリサルタン・イソプロキシル非晶形とその調製方法及びその非晶形を含む医薬組成物

Also Published As

Publication number Publication date
AU2003209669A1 (en) 2004-09-17

Similar Documents

Publication Publication Date Title
CA2717326C (fr) Preparation de lenalidomide
AU2001257213B2 (en) Zolpidem hemitartrate
US8686153B2 (en) Lenalidomide salts
US20150018386A1 (en) Amorphous form of apixaban, process of preparation and compositions thereof
US20100081809A1 (en) Amorphous valganciclovir hydrochloride
WO2006076561A1 (fr) Procede de preparation de valsartan amorphe
WO2018109786A1 (fr) Nouveaux polymorphes et sels de dérivés de carbamoyle pyridone polycycliques
WO2004076443A1 (fr) Forme amorphe de potassium de losartan
WO2017130219A1 (fr) Dispersion solide amorphe de palbociclib
WO2004087681A1 (fr) Nouvelle forme amorphe du valsartan
US7777049B2 (en) Crystalline forms of Rizatriptan benzoate
AU693939B2 (en) Novel crystal forms of 1-(5-methanesulfonamidoindolyl-2- carbonyl)-4-(3-(1-methylethylamino)-2-pyridinyl) piperazine
WO2018078383A1 (fr) Composition pharmaceutique comprenant du selexipag amorphe
EP1473036B1 (fr) Zolpidem hemitartrate comme solvate
ZA200208454B (en) Zolpidem hemitartrate.
EP2146958A1 (fr) Procédé de préparation de la forme a du tégasérode

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 709/CHENP/2003

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2003/01090

Country of ref document: TR

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2005/03400

Country of ref document: TR

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Ref document number: JP